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Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress

2021; Nature Portfolio; Volume: 11; Issue: 1 Linguagem: Inglês

10.1038/s41598-021-88944-8

2045-2322

Átila Duque Rossi, João Locke Ferreira de Araújo, Tailah Bernardo de Almeida, Marcelo Ribeiro-Alves, Camila de Almeida Velozo, Jéssica Maciel de Almeida, Isabela de Carvalho Leitão, Sâmila Natiane Ferreira, Jéssica da Silva Oliveira, Hugo José Alves, Helena Toledo Scheid, Débora S. Faffe, Rafael Mello Galliez, Renata Eliane de Ávila, Gustavo Gomes Resende, Mauro M. Teixeira, Alice Laschuk Herlinger, Aliny dos Santos Carvalho, André F. Santos, Anna Carla Pinto Castiñeiras, Bianca Isabelle Barreto Teixeira, Bianca Ortiz da Silva, Bruno Clarkson, Bruno Eduardo Dematté, Camila Nacif, Camille Victória Leal Correia de Silva, Carolina Moreira Voloch, Caroline Macedo Nascimento, Carolyne Lalucha Alves L. da Graça, Cássia Cristina Alves Gonçalves, Cíntia Policarpo, Diana Mariani, Ekaterini Simões Goudouri, Elaine Sobral da Costa, Elisângela Silva, Enrico Bruno Riscarolli, Érica Ramos dos Santos Nascimento, Fabio Hecht Castro Medeiros, Fábio L. Monteiro, Fernanda Leitão dos Santos, Fernando Luz de Castro, Filipe Romero Rebello Moreira, Francine Bittencourt Schiffler, Gabriela Bergiante Kraychete, Gabriele Silveira da Cunha, Gisely Novaes Borges da Cunha, Guilherme S. Lira, Gustavo Peixoto Duarte da Silva, Harrison James Westgarth, Helena D.’Anunciação de Oliveira, Helena Keito Toma, Huang Fang, Inês Corrêa Gonçalves, Ingrid Camelo da Silva, Isabela Labarba Carvalho de Almeida, Joissy Aprigio de Oliveira, Juliana Cazarin de Menezes, Juliana T.S. Fortuna, Karyne Ferreira Monteiro, Kíssyla Harley Della Pascôa França, Laura Zalcberg Renault, Lendel Correia da Costa, Leticia Averbug Correa, Liane de Jesus Ribeiro, Lídia Theodoro Boullosa, Liliane Cavalcante, Luana dos Santos Costa, Lucas Matos Millioni, Luciana Jesus da Costa, Luiza M. Higa, Marcela dos Santos Durães, Marcelo Amaral de Souza, Marcelo Calado de Paula Tôrres, Mariana Freire Campos, Mariana Quinto, Mariane Talon de Menezes, Marisa Souza Correia, Mateus Rodrigues de Queiroz, Matheus Augusto Calvano Cosentino, Mayla Gabryele Miranda de Melo, Mirela D’arc Ferreira da Costa, Pedro Paz, Raíssa Mirella dos Santos Cunha da Costa, Raquel Fernandes Coelho, Richard Araújo Maia, Rodrigo Brindeiro, Romina Carvalho Ferreira, Sérgio Machado Lisboa, Thamiris dos Santos Miranda, Victor Akira Ota, Victoria Cortes Bastos, Viviane Guimarães Gomes, Orlando da Costa Ferreira Júnior, Terezinha Marta Pereira Pinto Castiñeiras, Renan P. Souza, Amílcar Tanuri, Renato Santana Aguiar, Shana Priscila Coutinho Barroso, Cynthia Chester Cardoso,

Long-Term Effects of COVID-19

Abstract ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case–control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome ( adj OR = 0.30; 95% CI 0.09–0.91), while TMPRSS2/ACE2 ratio was associated with risk ( adj OR = 4.28; 95% CI 1.36–13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.